This project considers certain features of aging cells and tissues. The first portion relates to the action of certain mixed function oxidases and their behavior in aging cells and tissues. Certain drugs, such as phenytoin, which are inducers of mixed function oxidases, are also investigated. The second project examines the role of vitamin K-dependent synthesis of a bone protein, osteocalcin, which contains gamma-carboxyglutamic acid. This process may have some role in the etiology of senile osteoporosis and other bone disorders. The third project examines the low density lipoprotein receptors in aging fibroblasts as well as the cell age dependence in the regulation of cholesterol biosynthesis. Evidence indicates that the number of LDL receptors decreases with the age of diploid fibroblast. The polyisoprenoid alkylation of certain compounds such as menadione is also studied in the aging fibroblast system. The fourth project examines various x-linked parameters as indices of cell aging. It also is involved with the examination of certain post-translational modifications which may be related to the cell cycle. In general, this program examines a variety of cell and tissue "age" dependent properties which could be of considerable importance in geriatric medicine and in the understanding of maturity onset disorders.